Gain-of-Function Mutations in the V2 Vasopressin Receptor

Abstract

Background: Excessive antidiuresis with resulting water overload and hyponatremia are principal features of the syndrome of inappropriate secretion of antidiuretic hormone, a condition of abnormal water balance associated with a wide variety of clinical disorders. Despite clinical and laboratory evaluations consistent with the syndrome of inappropriate secretion of antidiuretic hormone, some patients may present with undetectable arginine vasopressin levels. In such cases, genetic studies may reveal novel activating mutations of the G-protein-coupled V2 vasopressin receptor, leading to what we term nephrogenic syndrome of inappropriate antidiuresis (NSIAD). We review the clinical and laboratory features of disordered water balance associated with such mutations in two pediatric NSIAD cases. Conclusions: Further characterization of NSIAD should enhance our understanding of fluid homeostasis and of clinical disease involving disorders of water balance.